Antiinflammatory drugs are most commonly used for the treatment of such chronic diseases as rheumatism and arthritis. Since such treatment is inherently on a long-term basis, irritating side effects caused by such drugs may be accentuated due simply to the long-term dosage which must be administered. Further, many antiinflammatory drugs contain carboxylic acid groups, which are in close proximity to an aryl substituent; such a configuration in the structure of the drug is thought to inhibit the release of those prostaglandins which are responsible for the maintenance of a healthy intestinal mucosa. Accordingly, many antiinflammatory drugs are associated with gastrointestinal irritation leading to abdominal pain, exacerbation of any existing ulcerous condition and possibly even creation of an ulcerous condition.
It is known that esterified acyl groups fail to exhibit this deleterious effect if the ester is not hydrolyzed in the gastrointestinal tract, but is hydrolyzed after being absorbed into the bloodstream. See, for example, Arzneimeittel Forschung, 8a/1980: 1424, which discloses that acemetacin, an oxy ester, is relatively non-irritating in the gastrointestinal tract in comparison with the corresponding free acid indomethacin. Also, see U.S. Pat. No. 3,988,446 which discloses glycerides esterified to antiinflammatory acids, to achieve a similar effect.
The present invention utilizes thioester derivatives thus utilizing their stability in the acidic conditions of the stomach. As they are absorbed into the bloodstream, and as such hydrolysis occurs there, the antiinflammatory effect then arises without the gastrointestinal irritation.
(The compounds may also be applied topically. Of course, in this case, gastrointestinal irritation is not relevant; but the compounds of the invention are here advantageous in that they are more expeditiously absorbed by the subject than the unesterified drug.)